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1.
Int J Audiol ; 61(10): 826-831, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34751079

RESUMO

OBJECTIVE: To study the impact of cardiovascular diseases (CVDs) on hearing deterioration among ageing adults in a longitudinal setting. Furthermore, to describe the pure tone threshold changes at the 0.125-8 kHz frequency range over 13 years. DESIGN: A population-based follow-up study. STUDY SAMPLE: A random sample of 850 adults, of whom 559 participated in the follow-up study. Otological examination, a structured interview, and pure tone audiometry were conducted. Multivariate regression models were used to estimate the effect of CVD (participants had at least one cardiovascular condition) on hearing deterioration of the better ear hearing level (BEHL), defined as a change in the pure-tone average (PTA) of the frequencies 0.5, 1, 2, and 4 kHz and separately at the lower (0.125, 0.25, and 0.5 kHz) and higher (4, 6, and 8 kHz) frequencies. RESULTS: In the multivariable-adjusted analysis, the BEHL change at 13 years was 0.7 dB greater among participants with CVD (p = 0.3). The mean BEHL change during the 13-year follow-up was 12.0 dB (95% CI 11.4-12.6) among all participants. CONCLUSIONS: No significant association between CVD and hearing threshold changes was found.


Assuntos
Doenças Cardiovasculares , Perda Auditiva , Audiometria de Tons Puros , Limiar Auditivo , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Seguimentos , Audição , Perda Auditiva/diagnóstico , Humanos
2.
Int J Circumpolar Health ; 80(1): 1925445, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33970828

RESUMO

The objective was to investigate work satisfaction among recently graduated otorhinolaryngologist - head and neck surgeons - (ENT surgeons). An electronic questionnaire was sent to all ENT surgeons graduated in Finland during a ten-year period. Answers about work satisfaction were analyzed in detail with regards to age, gender, university of specialist training, experience, place of work and further education.Altogether 125/129 (96.9%) responded. The majority (87.8%) of the respondents enjoyed their current main occupation. The older age group (≥40 vs <40 years) was more satisfied (93.7% vs. 81.7%; p=0.042). Consultation opportunities and workplace atmosphere were reported as good by 85.6% and 90.4% of the respondents, respectively. Training opportunities were considered good by 82.4%, albeit by only 60% of the private physicians (p=0.047). Private sector practitioners were also less satisfied with the versatility of their work (p<0.001). Work at a university hospital was considered more strenuous (p<0.001). Over half (54.8%) felt insecure about continuation of their employment status. Most of the recently graduated Finnish ENT surgeons are satisfied with their current occupation, consultation opportunities and workplace atmosphere. However, work at university hospitals in particular was considered often strenuous and over half of the respondents felt insecure about the continuity of their employment.


Assuntos
Satisfação Pessoal , Cirurgiões , Idoso , Emprego , Finlândia , Humanos , Satisfação no Emprego , Inquéritos e Questionários
3.
J Oral Maxillofac Surg ; 79(6): 1384.e1-1384.e5, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33811825

RESUMO

PURPOSE: Head and neck cancer requiring free-flap reconstruction is associated with relatively high mortality. We aimed to evaluate perioperative risk factors for 1-year mortality in this patient group. METHODS: This is a single-center retrospective analysis of 204 patients operated during 2008 to 2018. RESULTS: A total of 47 (23.0%) patients died within 1 year. In univariate analysis, there were no differences in the intraoperative course between 1-year survivors and nonsurvivors. Among the 1-year nonsurvivors, preoperative albumin level was lower (39 [36 to 43] vs 42 [39 to 44], P = .032) and the Sequential Organ Failure Assessment admission score was higher (4 [3 to 5] vs 3 [2 to 4], P = .003) than those of the 1-year survivors. Among the nonsurvivors, the preoperative and postoperative levels of leukocytes were higher (7.6 [6.7 to 9.5] vs 6.9 [5.5 to 8.4], P = .002; 11.4 [9.0 to 14.2] vs 8.7 [7.2 to 11.3], P < .001). The highest odds ratios for 1-year mortality in multivariate analysis were American Society of Anesthesiologists A classification greater than 2 (3.9 CI 1.4 to 10.5), male gender (4.0 CI 1.5 to 11), and increase in leukocyte count (1.3 CI 1.1 to 1.5). CONCLUSIONS: One-year nonsurvivors had higher American Society of Anesthesiologists classification and were more often men. The postoperative inflammatory markers were higher in nonsurvivors, while the intraoperative course did not have a significant impact on the 1-year mortality.


Assuntos
Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Procedimentos de Cirurgia Plástica , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Masculino , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores de Risco
4.
Int J Audiol ; 60(9): 687-694, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33426978

RESUMO

OBJECTIVE: The aim of this study was to investigate the prevalence and incidence of hearing impairment (HI) in a longitudinal setting among adults. DESIGN: An unscreened, population-based epidemiological 13-year follow-up study. Study sample: 850 randomly sampled 54 to 66-year-old baseline participants, of whom 559 participated in the follow-up study at the age of 68 to 79 years. A questionnaire-based interview, an otological examination and pure-tone audiometry were performed. RESULTS: The overall prevalence of HI was 70.3%, defined by better ear hearing level (BEHL) ≥ 20 dB in the 0.5-4 kHz frequency range. The prevalence was higher among men (78.6%) than among women (63.7%). The overall incidence rate for HI was 45.8 per 1000 person years and the 13-year cumulative incidence was 60.9%. The incidence was higher among men and older participants. CONCLUSION: HI is highly prevalent and incident among older adults in Northern Finland.


Assuntos
Perda Auditiva , Idoso , Audiometria de Tons Puros , Feminino , Seguimentos , Perda Auditiva/diagnóstico , Perda Auditiva/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência
5.
Int J Circumpolar Health ; 79(1): 1715710, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-31967532

RESUMO

We determined the employment status of recently graduated otorhinolaryngologist-head and neck surgeons (ENT doctors) in Finland during the past 10 years. We also investigated the job vacancy rate of the Departments of Otorhinolaryngology-Head and Neck Surgery (Department of ORL-HNS). An electronic questionnaire was sent to all ENT doctors who had graduated during 2007-2017 and to chief physicians of all Departments of ORL-HNS. Chi-square and Fisher's test were used in the analyses. Altogether 129 ENT doctors had graduated and 125 (96.9%) responded. Thirty (24%) physicians had been employed in a position that did not correspond to their ENT doctor training. All 30 chief physicians responded and a total of 306 physicians were working at their departments (215 ENT doctors, 91 residents). However, there were only 241 available positions (197 for ENT doctors, 44 for residents). It was estimated that 65 ENT doctors would retire within 10 years. At the moment there does not seem to be a significant shortage of ENT doctors in Finland. The current national volume of resident intake in the ENT training programme is twofold in comparison with the estimated retirement rate in the public sector.


Assuntos
Emprego/estatística & dados numéricos , Internato e Residência/estatística & dados numéricos , Otolaringologia/estatística & dados numéricos , Finlândia , Humanos , Procedimentos Cirúrgicos Otológicos/estatística & dados numéricos , Recursos Humanos
6.
Int J Circumpolar Health ; 76(1): 1398004, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29132251

RESUMO

The Saami are the only indigenous population in Europe and their traditional living area is northern Scandinavia. Hearing impairment (HI) among Saami has not been studied before. The objective was to investigate the presence and type of HI among Saami adults, aged 49-77 years (median age 61 years), living in northern Finland. In addition, the presence of self-reported hearing difficulties, difficulties to hear in background noise and tinnitus were studied. An epidemiological, cross-sectional study encompassing a structured interview, otological examination and audiometry was performed. Bilateral HI was present in 42.9% of men and 29.4% of women, when HI was defined as a pure tone average (PTA) of at least 20 dB hearing level (HL) or more at the frequencies of 0.5, 1, 2 and 4 kHz. In one or both ears (worse ear hearing level, WEHL0.5,1,2,4≥20 dB HL) HI was present in 61.8% of men and 42.2% of women. Sensorineural high frequency hearing impairment was found to be most common. Nearly half (46.9%) of the study subjects reported hearing problems and more than half (55.6%) reported difficulties in following conversation in background noise. Measured HI and subjective hearing difficulties are common among the Saami adults. The healthcare personnel working in this area should be aware of the hearing problems of the Saami population. ABBREVIATIONS: ARHI, Age-related hearing impairment; PTA, Pure tone average; HI, Hearing impairment; HL, Hearing level; BEHL, Better ear hearing level; WEHL, Worse ear hearing level; CI, Confidence interval.


Assuntos
Perda Auditiva/etnologia , População Branca/estatística & dados numéricos , Idoso , Regiões Árticas/epidemiologia , Estudos Transversais , Orelha/anatomia & histologia , Feminino , Finlândia/epidemiologia , Perda Auditiva Neurossensorial/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Autorrelato , Zumbido/etnologia
7.
Hear Res ; 355: 97-101, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28974383

RESUMO

Wolfram syndrome (WS) is caused by recessive mutations in the Wolfram syndrome 1 (WFS1) gene. Sensorineural hearing impairment (HI) is a frequent feature in WS and, furthermore, certain mutations in WFS1 cause nonsyndromic dominantly inherited low-frequency sensorineural HI. These two phenotypes are clinically distinct indicating that WFS1 is a reasonable candidate for genetic studies in patients with other phenotypes of HI. Here we have investigated, whether the variation in WFS1 has a pathogenic role in age-related hearing impairment (ARHI). WFS1 gene was investigated in a population sample of 518 Finnish adults born in 1938-1949 and representing variable hearing phenotypes. Identified variants were evaluated with respect to pathogenic potential. A rare mutation predicted to be pathogenic was found in a family with many members with impaired hearing. Twenty members were recruited to a segregation study and a detailed clinical examination. Heterozygous p.Tyr528His variant segregated completely with late-onset HI in which hearing deteriorated first at high frequencies and progressed to mid and low frequencies later in life. We report the first mutation in the WFS1 gene causing late-onset HI with audiogram configurations typical for ARHI. Monogenic forms of ARHI are rare and our results add WFS1 to the short list of such genes.


Assuntos
Perda Auditiva Neurossensorial/genética , Audição/genética , Proteínas de Membrana/genética , Mutação , Presbiacusia/genética , Estimulação Acústica , Adolescente , Adulto , Fatores Etários , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Audiometria de Tons Puros , Análise Mutacional de DNA , Feminino , Finlândia , Predisposição Genética para Doença , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/fisiopatologia , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Presbiacusia/diagnóstico , Presbiacusia/fisiopatologia , Adulto Jovem
8.
Int J Audiol ; 54(4): 265-73, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25547009

RESUMO

OBJECTIVE: To investigate the influence of cardiovascular diseases on hearing impairment (HI) among adults. Furthermore, to seek other potential risk factors for HI, such as smoking, obesity, and socioeconomic class. DESIGN: A cross-sectional, unscreened, population-based, epidemiological study among adults. STUDY SAMPLE: The subjects (n = 850), aged 54-66 years, were randomly sampled from the population register. A questionnaire survey, an otological examination, and pure-tone audiometry were performed. RESULTS: Cardiovascular diseases did not increase the risk for HI in a propensity-score adjusted logistic regression model: OR 1.24, 95% CI 0.79 to 1.96 for HI defined by better ear hearing level (BEHL), and OR 1.48, 95% CI 0.96 to 2.28 for HI defined by worse ear hearing level (WEHL), in the 0.5-4 kHz frequency range. Heavy smoking is a risk factor for HI among men (BEHL: OR 1.96, WEHL: OR 1.88) and women (WEHL: OR 2.4). Among men, obesity (BEHL, OR 1.85) and lower socioeconomic class (BEHL: OR 2.79, WEHL: OR 2.28) are also risk factors for HI. CONCLUSION: No significant association between cardiovascular disease and HI was found.


Assuntos
Doenças Cardiovasculares/complicações , Perda Auditiva/etiologia , Idoso , Audiometria de Tons Puros , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Pontuação de Propensão , Fatores de Risco , Fumar/efeitos adversos , Fatores Socioeconômicos , Inquéritos e Questionários
9.
J Am Acad Audiol ; 25(4): 415, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25126689
10.
Otol Neurotol ; 34(5): 838-44, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23739559

RESUMO

OBJECTIVE: To investigate the familial correlations and intraclass correlation of age-related hearing impairment (ARHI) in specific frequencies. In addition, heritability estimates were calculated. STUDY DESIGN: Multicenter survey in 8 European centers. SUBJECTS: One hundred ninety-eight families consisting of 952 family members, screened by otologic examination and structured interviews. Subjects with general conditions, known to affect hearing thresholds or known otologic cause were excluded from the study. RESULTS: We detected familial correlation coefficients of 0.36, 0.37, 0.36, and 0.30 for 0.25, 0.5, 1, and 2 kHz, respectively, and correlation coefficients of 0.20 and 0.18 for 4 and 8 kHz, respectively. Variance components analyses showed that the proportion of the total variance attributable to family differences was between 0.32 and 0.40 for 0.25, 0.5, 1, and 2 kHz and below 0.20 for 4 and 8 kHz. When testing for homogeneity between sib pair types, we observed a larger familial correlation between female than male subjects. Heritability estimates ranged between 0.79 and 0.36 across the frequencies. DISCUSSION: Our results indicate that there is a substantial shared familial effect in ARHI. We found that familial aggregation of ARHI is markedly higher in the low frequencies and that there is a trend toward higher familial aggregation in female compared with male subjects.


Assuntos
Audiometria de Tons Puros/estatística & dados numéricos , Limiar Auditivo/fisiologia , Perda Auditiva/epidemiologia , Fatores Etários , Idoso , Análise de Variância , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
Int J Audiol ; 51(11): 833-40, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22934931

RESUMO

OBJECTIVE: To investigate the prevalence of ear diseases, other otological risk factors potentially affecting hearing, and noise exposure among adults. Furthermore, subject-related factors possibly associated with hearing impairment (HI), i.e. handedness, eye color, and susceptibility to sunburn, were studied. DESIGN: A cross-sectional, unscreened, population-based, epidemiological study among adults. STUDY SAMPLE: The subjects (n = 850), aged 54-66 years, were randomly sampled from the population register. A questionnaire survey, an otological examination, and pure-tone audiometry were performed. RESULTS: Chronic middle-ear disease (both active and inactive) was the most common ear disease with a prevalence of 5.3%, while the prevalence of otosclerosis was 1.3%, and that of Ménière's disease, 0.7%. Noise exposure was reported by 46% of the subjects, and it had no effect on hearing among those with no ear disease or other otological risk factors for HI. Dark eye color and non-susceptibility to sunburn were associated with HI among noise-exposed subjects. CONCLUSIONS: Common ear diseases and other otological risk factors constitute a major part of the etiologies of HI among adults. Contrary to previous studies, noise exposure turned out to have only marginal effect on hearing among those with no otological risk factors.


Assuntos
Otopatias/epidemiologia , Perda Auditiva/epidemiologia , Idoso , Audiometria de Tons Puros , Estudos Transversais , Exposição Ambiental/estatística & dados numéricos , Europa (Continente)/epidemiologia , Cor de Olho , Feminino , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Ruído , Otoscopia , Prevalência , Sistema de Registros , Fatores de Risco , Queimadura Solar/epidemiologia , Inquéritos e Questionários
12.
J Am Acad Audiol ; 22(8): 550-9, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22031679

RESUMO

BACKGROUND: There are not many population-based epidemiological studies on the association between self-reported hearing problems and measured hearing thresholds in older adults. Previous studies have shown that the relationship between self-reported hearing difficulties and measured hearing thresholds is unclear and, according to our knowledge, there are no previous population-based studies reporting hearing thresholds among subjects with hyperacusis. PURPOSE: The aim was to investigate the prevalence of self-reported hearing problems, that is, hearing difficulties, difficulties in following a conversation in noise, tinnitus, and hyperacusis, and to compare the results with measured hearing thresholds in older adults. RESEARCH DESIGN: Cross-sectional, population-based, and unscreened. STUDY SAMPLE: Random sample of subjects (n=850) aged 54-66 yr living in the city of Oulu (Finland) and the surrounding areas. DATA COLLECTION AND ANALYSIS: Otological examination, pure tone audiometry, questionnaire survey RESULTS: The prevalence of self-reported hearing problems was 37.1% for hearing difficulties, 43.3% for difficulties in following a conversation in noise, 29.2% for tinnitus, and 17.2% for hyperacusis. More than half of the subjects had no hearing impairment, or HI (BEHL[better ear hearing level]0.5-4 kHz<20 dB HL) even though they reported hearing problems. Subjects with self-reported hearing problems, including tinnitus and hyperacusis, had significantly poorer hearing thresholds than those who did not report hearing problems. Self-reported hearing difficulties predicted hearing impairment in the pure-tone average at 4, 6, and 8 kHz, and at the single frequency of 4 kHz. CONCLUSIONS: The results indicate that self-reported hearing difficulties are more frequent than hearing impairment defined by audiometric measurement. Furthermore, self-reported hearing difficulties seem to predict hearing impairment at high frequencies (4-8 kHz) rather than at the frequencies of 0.5-4 kHz, which are commonly used to define the degree of hearing impairment in medical and legal issues.


Assuntos
Perda Auditiva/diagnóstico , Perda Auditiva/epidemiologia , Hiperacusia/diagnóstico , Hiperacusia/epidemiologia , Zumbido/diagnóstico , Zumbido/epidemiologia , Idoso , Audiometria de Tons Puros/estatística & dados numéricos , Limiar Auditivo , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Distribuição Aleatória , Autorrelato , Inquéritos e Questionários
13.
Int J Audiol ; 50(11): 793-801, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21916791

RESUMO

OBJECTIVE: There are only a few population-based epidemiological studies on audiogram configurations among adults. The aim of this study was to investigate the prevalence of different audiogram configurations among older adults. In addition, audiogram configurations among subjects reporting hearing problems were examined. DESIGN: Cross-sectional, population-based, unscreened epidemiological study among older adults. STUDY SAMPLE: The subjects (n = 850), aged 54-66 years, were randomly sampled from the population register. A questionnaire survey, an otological examination, and pure-tone audiometry were performed. RESULTS: The most prevalent audiogram configuration among men was high-frequency steeply sloping (65.3% left ear, 51.2% right ear) and among women, high-frequency gently sloping (33.0% left ear, 31.5% right ear). There were significantly more flat configurations among women than among men. Unclassified audiograms were common especially among women (17.5%). Subjects reporting hearing difficulties, difficulties in following conversation in noise, or tinnitus, more often had a high-frequency steeply sloping configuration than those not reporting. CONCLUSIONS: High-frequency sloping audiogram configurations were common among older adults, and a high-frequency steeply sloping configuration was common among those reporting hearing problems.


Assuntos
Audiometria de Tons Puros , Vias Auditivas/fisiopatologia , Transtornos da Audição/diagnóstico , Transtornos da Audição/epidemiologia , Autorrelato , Estimulação Acústica , Fatores Etários , Idoso , Análise de Variância , Limiar Auditivo , Condução Óssea , Distribuição de Qui-Quadrado , Estudos Transversais , Feminino , Finlândia/epidemiologia , Transtornos da Audição/fisiopatologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Sistema de Registros , Fatores Sexuais
14.
Eur J Hum Genet ; 19(3): 347-52, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21150888

RESUMO

The understanding of patterns of genetic variation within and among human populations is a prerequisite for successful genetic association mapping studies of complex diseases and traits. Some populations are more favorable for association mapping studies than others. The Saami from northern Scandinavia and the Kola Peninsula represent a population isolate that, among European populations, has been less extensively sampled, despite some early interest for association mapping studies. In this paper, we report the results of a first genome-wide SNP-based study of genetic population structure in the Finnish Saami. Using data from the HapMap and the human genome diversity project (HGDP-CEPH) and recently developed statistical methods, we studied individual genetic ancestry. We quantified genetic differentiation between the Saami population and the HGDP-CEPH populations by calculating pair-wise F(ST) statistics and by characterizing identity-by-state sharing for pair-wise population comparisons. This study affirms an east Asian contribution to the predominantly European-derived Saami gene pool. Using model-based individual ancestry analysis, the median estimated percentage of the genome with east Asian ancestry was 6% (first and third quartiles: 5 and 8%, respectively). We found that genetic similarity between population pairs roughly correlated with geographic distance. Among the European HGDP-CEPH populations, F(ST) was smallest for the comparison with the Russians (F(ST)=0.0098), and estimates for the other population comparisons ranged from 0.0129 to 0.0263. Our analysis also revealed fine-scale substructure within the Finnish Saami and warns against the confounding effects of both hidden population structure and undocumented relatedness in genetic association studies of isolated populations.


Assuntos
Etnicidade/genética , Estudos de Associação Genética/métodos , Genética Populacional , Genoma Humano , Polimorfismo de Nucleotídeo Único , População Branca/genética , Povo Asiático/genética , Mapeamento Cromossômico , Humanos , Modelos Genéticos , Países Escandinavos e Nórdicos
15.
Int J Audiol ; 49(12): 920-7, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20839902

RESUMO

There are only a few large, population-based epidemiological studies on hearing impairment (HI) in adults. The objective of this study was to investigate the prevalence of HI and possible differences between ears in older adults. The subjects (n = 850), aged 54-66 years, were randomly sampled from the population register. A questionnaire survey, an otological examination, and pure-tone audiometry were performed. Another questionnaire was mailed to collect information on non-participants. The prevalence of HI averaged over the frequencies of 0.5, 1, 2, and 4 kHz for the better ear ≥20 dB HL was 26.7% (men: 36.8%, women: 18.4%). There was no difference between left and right ear pure-tone averages over the frequencies 0.5, 1, 2, and 4 kHz (PTA(0.5-4 kHz)), but a significant difference of -0.8 dB HL was found for the low frequencies 0.125, 0.25, and 0.5 kHz (PTA(0.125-0.5 kHz)), and 4.4 dB HL for the high frequencies over 4, 6, and 8 kHz (PTA(4-8 kHz)). In conclusion, HI was a highly prevalent finding in this age group.


Assuntos
Perda Auditiva/epidemiologia , Audição , Estimulação Acústica , Distribuição por Idade , Idoso , Audiometria de Tons Puros , Limiar Auditivo , Estudos Transversais , Feminino , Finlândia/epidemiologia , Inquéritos Epidemiológicos , Perda Auditiva/diagnóstico , Perda Auditiva/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Distribuição por Sexo , Inquéritos e Questionários
16.
Eur J Hum Genet ; 18(6): 685-93, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20068591

RESUMO

This study aimed at contributing to the elucidation of the genetic basis of age-related hearing impairment (ARHI), a common multifactorial disease with an important genetic contribution as demonstrated by heritability studies. We conducted a genome-wide association study (GWAS) in the Finnish Saami, a small, ancient, genetically isolated population without evidence of demographic expansion. The choice of this study population was motivated by its anticipated higher extent of LD, potentially offering a substantial power advantage for association mapping. DNA samples and audiometric measurements were collected from 352 Finnish Saami individuals, aged between 50 and 75 years. To reduce the burden of multiple testing, we applied principal component (PC) analysis to the multivariate audiometric phenotype. The first three PCs captured 80% of the variation in hearing thresholds, while maintaining biologically important audiometric features. All subjects were genotyped with the Affymetrix 100 K chip. To account for multiple levels of relatedness among subjects, as well as for population stratification, association testing was performed using a mixed model. We summarised the top-ranking association signals for the three traits under study. The top-ranked SNP, rs457717 (P-value 3.55 x 10(-7)), was associated with PC3 and was localised in an intron of the IQ motif-containing GTPase-activating-like protein (IQGAP2). Intriguingly, the SNP rs161927 (P-value 0.000149), seventh-ranked for PC1, was positioned immediately downstream from the metabotropic glutamate receptor-7 gene (GRM7). As a previous GWAS of a European and Finnish sample set already suggested a role for GRM7 in ARHI, this study provides further evidence for the involvement of this gene.


Assuntos
Perda Auditiva/genética , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Envelhecimento/fisiologia , Feminino , Finlândia/epidemiologia , Frequência do Gene , Estudo de Associação Genômica Ampla , Perda Auditiva/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptores de Glutamato Metabotrópico/genética , Receptores de Glutamato Metabotrópico/fisiologia , Países Escandinavos e Nórdicos/etnologia , Estudos de Validação como Assunto , Proteínas Ativadoras de ras GTPase/genética , Proteínas Ativadoras de ras GTPase/fisiologia
17.
Eur J Hum Genet ; 18(5): 569-74, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19935831

RESUMO

The Saami from Fennoscandia are believed to represent an ancient, genetically isolated population with no evidence of population expansion. Theoretical work has indicated that under this demographic scenario, extensive linkage disequilibrium (LD) is generated by genetic drift. Therefore, it has been suggested that the Saami would be particularly suited for genetic association studies, offering a substantial power advantage and allowing more economic study designs. However, no study has yet assessed this claim. As part of a GWAS for a complex trait, we evaluated the relative power for association studies of common variants in the Finnish Saami. LD patterns in the Saami were very similar to those in the non-African HapMap reference panels. Haplotype diversity was reduced and, on average, levels of LD were higher in the Saami as compared with those in the HapMap panels. However, using a 'hidden' SNP approach we show that this does not translate into a power gain in association studies. Contrary to earlier claims, we show that for a given set of common SNPs, genomic coverage attained in the Saami is similar to that in the non-African HapMap panels. Nevertheless, the reduced haplotype diversity could potentially facilitate gene identification, especially if multiple rare variants play a role in disease etiology. Our results further indicate that the HapMap is a useful resource for genetic studies in the Saami.


Assuntos
Etnicidade/genética , Estudos de Associação Genética/métodos , Genoma Humano/genética , Polimorfismo de Nucleotídeo Único/genética , População Branca/genética , Idoso , Cromossomos Humanos Par 18/genética , Finlândia , Frequência do Gene/genética , Haplótipos/genética , Humanos , Desequilíbrio de Ligação/genética , Pessoa de Meia-Idade
18.
Am J Hum Genet ; 83(3): 401-7, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18760390

RESUMO

Age-related hearing impairment (ARHI), or presbycusis, is a very common multifactorial disorder. Despite the knowledge that genetics play an important role in the etiology of human ARHI as revealed by heritability studies, to date, its precise genetic determinants remain elusive. Here we report the results of a cross-sectional family-based genetic study employing audiometric data. By using principal component analysis, we were able to reduce the dimensionality of this multivariate phenotype while capturing most of the variation and retaining biologically important features of the audiograms. We conducted a genome-wide association as well as a linkage scan with high-density SNP microarrays. Because of the presence of genetic population substructure, association testing was stratified after which evidence was combined by meta-analysis. No association signals reaching genome-wide significance were detected. Linkage analysis identified a linkage peak on 8q24.13-q24.22 for a trait correlated to audiogram shape. The signal reached genome-wide significance, as assessed by simulations. This finding represents the first locus for an ARHI trait.


Assuntos
Envelhecimento/genética , Cromossomos Humanos Par 8/genética , Ligação Genética , Genoma Humano , Polimorfismo de Nucleotídeo Único , Presbiacusia/genética , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Presbiacusia/fisiopatologia , Análise de Componente Principal , Locos de Características Quantitativas
19.
J Assoc Res Otolaryngol ; 9(3): 264-76; discussion 261-3, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18543032

RESUMO

A multicenter study was set up to elucidate the environmental and medical risk factors contributing to age-related hearing impairment (ARHI). Nine subsamples, collected by nine audiological centers across Europe, added up to a total of 4,083 subjects between 53 and 67 years. Audiometric data (pure-tone average [PTA]) were collected and the participants filled out a questionnaire on environmental risk factors and medical history. People with a history of disease that could affect hearing were excluded. PTAs were adjusted for age and sex and tested for association with exposure to risk factors. Noise exposure was associated with a significant loss of hearing at high sound frequencies (>1 kHz). Smoking significantly increased high-frequency hearing loss, and the effect was dose-dependent. The effect of smoking remained significant when accounting for cardiovascular disease events. Taller people had better hearing on average with a more pronounced effect at low sound frequencies (<2 kHz). A high body mass index (BMI) correlated with hearing loss across the frequency range tested. Moderate alcohol consumption was inversely correlated with hearing loss. Significant associations were found in the high as well as in the low frequencies. The results suggest that a healthy lifestyle can protect against age-related hearing impairment.


Assuntos
Consumo de Bebidas Alcoólicas , Índice de Massa Corporal , Perda Auditiva/epidemiologia , Perda Auditiva/prevenção & controle , Ruído Ocupacional/efeitos adversos , Obesidade , Fumar/efeitos adversos , Fatores Etários , Idoso , Análise por Conglomerados , Europa (Continente) , Feminino , Inquéritos Epidemiológicos , Perda Auditiva/genética , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Fatores de Risco
20.
Hum Mol Genet ; 17(2): 159-69, 2008 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-17921507

RESUMO

Age-related hearing impairment (ARHI) is the most prevalent sensory impairment in the elderly. ARHI is a complex disease caused by an interaction between environmental and genetic factors. The contribution of various environmental factors has been relatively extensively studied. In contrast, investigations to identify the genetic risk factors have only recently been initiated. In this paper we describe the results of an association study performed on 2418 ARHI samples derived from nine centers from seven European countries. In 70 candidate genes, a total of 768 tag single nucleotide polymorphisms (SNPs) were selected based on HAPMAP data. These genes were chosen among the monogenic hearing loss genes identified in mice and men in addition to several strong functional candidates. After genotyping and data polishing, statistical analysis of all samples combined resulted in a P-value that survived correction for multiple testing for one SNP in the GRHL2 gene. Other SNPs in this gene were also associated, albeit to a lesser degree. Subsequently, an analysis of the most significant GRHL2 SNP was performed separately for each center. The direction of the association was identical in all nine centers. Two centers showed significant associations and a third center showed a trend towards significance. Subsequent fine mapping of this locus demonstrated that the majority of the associated SNPs reside in intron 1. We hypothesize that the causative variant may change the expression levels of a GRHL2 isoform.


Assuntos
Proteínas de Ligação a DNA/genética , Presbiacusia/genética , Fatores de Transcrição/genética , Idoso , Europa (Continente) , Predisposição Genética para Doença , Humanos , Íntrons , Desequilíbrio de Ligação , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Isoformas de Proteínas/genética
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